UMMS Affiliation

Department of Neurology

Publication Date


Document Type



Stroke; Thrombolytic Therapy; Granulocyte Colony-Stimulating Factor; Plasminogen Activators


Life Sciences | Medicine and Health Sciences | Neurology


BACKGROUND: Granulocyte Colony-Stimulating Factor (G-CSF) has remarkable neuroprotective properties. Due to its proven safety profile, G-CSF is currently used in clinical stroke trials. As neuroprotectants are considered to be more effective in the early phase of cerebral ischemia and during reperfusion, G-CSF should to be tested in combination with thrombolysis. Therefore, combination therapy was investigated in an experimental model of thromboembolic stroke.

METHODS: Male Wistar rats (n = 72) were subjected to a model of thromboembolic occlusion (TE) of the middle cerebral artery. Different groups (n = 12 each) treated by recombinant tissue-plasminogen activator (rt-PA) or/and G-CSF: group control (control), group early G-CSF (G-CSF 60 min after TE), group rt-PA (rt-PA 60 min after TE), group com (combination rt-PA/G-CSF), group delayed rt-PA (rt-PA after 180 min), group deco (G-CSF after 60 min, rt-PA after 180 min). Animals were investigated by magnetic resonance imaging (MRI) and silver infarct staining (SIS) 24 hours after TE.

RESULTS: Early G-CSF or rt-PA reduced the infarct size compared to all groups (p < 0.05 to p < 0.01) with the exception of group com, (p = n.s.) as measured by T2, DWI, and SIS. Late administration of rt-PA lead to high mortality and larger infarcts compared to all other groups (p < 0.05 to p < 0.01). Pre-treatment by G-CSF (deco) reduced infarct site compared to delayed rt-PA treatment (p < 0.05). G-CSF did not significantly influence PWI when combined with rt-PA. All animals treated by rt-PA showed improved parameters in PWI indicating reperfusion.

CONCLUSIONS: G-CSF was neuroprotective when given early after TE. Early combination with rt-PA showed no additional benefit compared to rt-PA or G-CSF alone, but did not lead to side effects. Pretreatment by G-CSF was able to reduce deleterious effects of late rt-PA treatment.

DOI of Published Version



Exp Transl Stroke Med. 2010 Apr 14;2:9. Link to article on publisher's site

Journal/Book/Conference Title

Experimental and translational stroke medicine

Related Resources

Link to Article in PubMed

PubMed ID




To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.